These studies investigate factors involved in differentiation, maintenance, and trafficking of T and B lymphocytes. Homeostasis of naive CD8 T cells relies on encounter with self MHC molecules. Previous work from our group and others indicate that T cells deprived of such cues change in their phenotype and exhibit Impaired survival: yet cells showing features of poor homeostasis are present at steady state in normal animals. In Aim 1, we investigate how such cells are maintained, and whether they play a distinct role in the response to foreign antigen. In Aims 2 and 3, we explore the function of the transcription factor KLF2 in T and B cells. Our preliminary data detected unexpected heterogeneity of KLF2 expression among certain subsets of memory CD4 and CDS T cells. Given KLF2's role in T cell trafficking and potentially in ceil quiescence, we will investigate the significance of KLF2 regulation on memory T cell subset localization and function. Lastly, in Aim 3, we build on surprising preliminary data indicating KLF2 is required for normal development of B cell subsets and is important for B cell functional responses. These studies will explore the impact of KLF2 in directing B cell differentiation and survival, as well as investigate the functional relevance of KLF2 regulated genes in B cell activation. RELEVANCE (See instmctions):